Correspondence
Treatment of Head and Neck Cancer
N Engl J Med 2008; 358:1076-1078March 6, 2008
- Article
To the Editor:
In the report by Posner et al. (Oct. 25 issue)1 on the treatment of head and neck cancer, we question the authors' implication that the 91-11 trial of the Radiation Therapy Oncology Group and Head and Neck Intergroup showed that cisplatin–fluorouracil (PF) induction followed by radiotherapy for laryngeal preservation is equivalent to or better than concomitant cisplatin and radiotherapy. The 91-11 trial was not designed to show equivalence.2 Both combinations resulted in better laryngectomy-free survival than did radiotherapy alone, but the composite end point does not account for a preserved larynx in patients whose death was not due to laryngeal cancer (over half the deaths). Rates of laryngeal preservation and locoregional control provide a much better assessment, and for both end points, the rates were significantly better with concomitant cisplatin and radiotherapy than with radiotherapy alone or PF induction followed by radiotherapy, whereas overall survival did not differ significantly.2,3 The results of the 91-11 trial do not justify the use of docetaxel–cisplatin–fluorouracil (TPF) sequential therapy for T3 and low-volume T4 laryngeal cancer.
Arlene Forastiere, M.D.
Johns Hopkins University School of Medicine, Baltimore, MD 21231
af@jhmi.edu Randal Weber, M.D.
Kian Ang, M.D., Ph.D.
M.D. Anderson Cancer Center, Houston, TX 77030Dr. Forastiere reports serving on the advisory board for Sanofi-Aventis; and Dr. Ang, serving on the advisory boards for and receiving honoraria from Sanofi-Aventis and Bristol-Myers Squibb. No other potential conflict of interest relevant to this letter was reported.
3 References1
Posner MR ,Hershock DM ,Blajman CR , et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357:1705-1715
Full Text | Web of Science | Medline2
Forastiere AA ,Goepfert H ,Maor M , et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091-2098
Full Text | Web of Science | Medline3
Forastiere AA ,Maor M ,Weber RS , et al. Long-term results of Intergroup RTOG 91-11: a phase III trial to preserve the larynx -- induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy. J Clin Oncol 2006;24:284s-284s
CrossRef | Web of Science
To the Editor:
We disagree with Posner and colleagues that induction chemotherapy with TPF plus chemoradiotherapy with carboplatin has been sufficiently tested to consider it a routine alternative to platinum-based concurrent chemoradiotherapy. We do not know the outcomes of ongoing phase 3 trials designed to address this controversy. The routine adoption of the sequential-therapy approach without level I evidence undermines the principle of equipoise and our ability to answer this important question.
Andy Trotti, III, M.D.
Moffitt Cancer Center, Tampa, FL 33612
andy.trotti@moffitt. org Thomas F. Pajak, Ph.D.
Radiation Therapy Oncology Group, Philadelphia, PA 19103John A. Ridge, M.D., Ph.D.
Fox Chase Cancer Center, Philadelphia, PA 19111Drs. Trotti and Ridge report serving on advisory boards for Sanofi-Aventis, and Dr. Trotti reports receiving speaking fees from Sanofi-Aventis. No other potential conflict of interest relevant to this letter was reported.
To the Editor:
In the studies of induction chemotherapy in the treatment of locally advanced head and neck cancer, reported by Vermorken et al. (also in the Oct. 25 issue)1 and Posner et al., cancer surgery was performed after chemoradiotherapy for patients requiring lymph-node dissection (e.g., patients with N3 disease), those with residual disease (either at the primary site or in the neck), or those who did not have a response to the treatment. However, only the report by Vermorken et al. provides the numbers of patients who underwent surgery; the authors state, “No significant difference was observed in the distribution between the two groups (P=0.22).” Since it is possible that an imbalance between the groups in the surgical consolidation rate may have had some effect on the outcome, we believe that Posner et al. should also have reported this information.
1 ReferencesFaisal Saghir, M.D.
Lawrence E. Feldman, M.D.
University of Illinois Cancer Center, Chicago, IL 60612
lawfeld@uic.edu 1
Vermorken JB ,Remenar E ,van Herpen C , et al. Cisplatin, fluorouracil, and docetaxil in unresectable head and neck cancer. N Engl J Med 2007;357:1695-1704
Full Text | Web of Science | Medline
To the Editor:
Posner et al. report a significantly increased 2-year survival rate (67% vs. 55%) for induction chemotherapy with TPF as compared with PF, followed by chemoradiotherapy with weekly carboplatin (area under the curve, 1.5), in patients with advanced head and neck cancer. Most of the trials included in the Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) that showed a survival benefit for concomitant chemotherapy used cisplatin.1 Analysis of records from 129 patients treated for stage III or IV head and neck cancer at Royal Marsden Hospital, in London, showed a 2-year survival rate of 63% with two cycles of PF followed by concomitant chemoradiotherapy with the use of cisplatin (100 mg per square meter of body-surface area on days 1 and 29). This schedule was delivered without a dose reduction in 86% of an unselected patient group.2 These data raise the possibility that the 12% absolute difference in the 2-year survival rates between groups in the TAX 324 study may have been due, at least in part, to the TPF regimen, which compensated for suboptimal chemoradiotherapy with low-dose weekly carboplatin rather than cisplatin in the PF regimen. Therefore, docetaxel-based induction TPF chemotherapy may not be beneficial when followed by concomitant cisplatin-containing chemoradiotherapy.
2 ReferencesChristopher M. Nutting, M.D.
Royal Marsden Hospital, London SW3 6JJ, United Kingdom
chris.nutting@rmh. nhs. uk Shreerang A. Bhide, M.R.C.P., F.R.C.R.
Kevin J. Harrington, Ph.D.
Institute of Cancer Research, London SW3 6JB, United Kingdom1
Pignon JP ,Bourhis J ,Domenge C ,Designe L . Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. Lancet 2000;355:949-955
CrossRef | Web of Science | Medline2
Bhide S ,Ahmed M ,Barbachano Y ,Harrington K ,Nutting CM . Neo-adjuvant chemotherapy followed by radical chemo-radiation in treatment of advanced head and neck cancer. Eur J Cancer 2007;5:Suppl:329-329
Author/Editor Response
Forastiere et al. question whether TPF should be considered a standard of care by asking whether laryngeal preservation is a more relevant end point than laryngectomy-free survival in the 91-11 trial. We believe that the original end point of the 91-11 trial, laryngectomy-free survival — alive with an intact larynx — is the more relevant end point of the trial. The 91-11 definition of laryngeal preservation includes patients who die from toxicity, those with locoregional recurrence, and those with treatment-related morbidity. We acknowledge that in the 91-11 trial, locoregional control was significantly better in the chemoradiotherapy group than in the PF-induction group, but chemoradiotherapy was associated with a relatively large number of treatment-related deaths, which are not counted in the definition of laryngeal preservation. Changing the end point from laryngectomy-free survival to laryngeal preservation led to the conclusion that chemoradiotherapy was associated with a positive outcome, but the most recent analysis1 revealed a similar and significant improvement in laryngectomy-free survival for PF and chemoradiotherapy (44% and 46%, respectively) as compared with radiotherapy alone (34%). We believe that being alive with an intact larynx (laryngectomy-free survival) is a clinically relevant end point and that our study shows the superiority of TPF over PF, suggesting that TPF might be expected to be better than chemoradiotherapy.
We disagree with Trotti et al. The three phase III studies comparing PF and chemoradiotherapy that have been performed to date all show equivalence of chemoradiotherapy and PF followed by radiotherapy for laryngectomy-free survival, overall survival, or both.2,3 In the absence of contrary data, we believe that sequential therapy with TPF is reasonable and is probably superior to chemoradiotherapy for locally advanced disease or for organ preservation.4 We agree with Trotti et al. that phase III trials must be completed. Equipoise based on currently available data, however, allows us to recommend either therapy as a reasonable alternative.
In response to the comments of Saghir and Feldman, surgery was an important component of therapy. Analysis of the effect of surgery on survival and organ preservation is ongoing.
Nutting et al. present interesting data; however, their unpublished, single-institution, non–protocol-driven experience does not allow for a robust comparison with data from phase III trials. Although their findings are suggestive, there is also suggestive phase III evidence that chemoradiotherapy with weekly carboplatin is equivalent to chemoradiotherapy with bolus cisplatin.5
5 ReferencesMarshall R. Posner, M.D.
Robert I. Haddad, M.D.
Roy B. Tishler, M.D., Ph.D.
Dana–Farber Cancer Institute, Boston, MA 02115
marshall_posner@dfci.harvard. edu 1
Forastiere AA ,Maor M ,Weber RS , et al. Long-term results of Intergroup RTOG 91-11: a phase III trial to preserve the larynx -- induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy. J Clin Oncol 2006;24:284s-284s
CrossRef | Web of Science2
Lefebvre J ,Horiot J ,Rolland F , et al. Phase III study on larynx preservation comparing induction chemotherapy and radiotherapy versus alternating chemoradiotherapy in resectable hypopharynx and larynx cancers: EORTC protocol 24954-22950. J Clin Oncol 2007;25:303s-303s3
Taylor SG IV ,Murthy AK ,Vannetzel JM , et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 1994;12:385-395
Web of Science | Medline4
Calais G ,Pointreau Y ,Alfonsi M , et al. Randomized phase III trial comparing induction chemotherapy using cisplatin (P) fluorouracil (F) with or without docetaxel (T) for organ preservation in hypopharynx and larynx cancer: preliminary results of GORTEC 2000-01. J Clin Oncol 2006;24:5506-55065
Chitapanarux I ,Lorvidhaya V ,Kamnerdsupaphon P , et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer 2007;43:1399-1406
CrossRef | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Vlad C. Sandulache, Jeffrey N. Myers, Robert L. Ferris. (2012) Altered metabolism in head and neck squamous cell carcinoma: an opportunity for identification of novel biomarkers and drug targets. Head & Neck 34:2, 282-290
CrossRef2
H.E. Eckel. (2012) Aktuelle Therapieoptionen bei Larynx- und Hypopharynxkarzinomen. HNO 60:1, 6-18
CrossRef3
Bagganahalli S. Somashekar, Pachiyappan Kamarajan, Theodora Danciu, Yvonne L. Kapila, Arul M. Chinnaiyan, Thekkelnaycke M. Rajendiran, Ayyalusamy Ramamoorthy. (2011) Magic Angle Spinning NMR-Based Metabolic Profiling of Head and Neck Squamous Cell Carcinoma Tissues. Journal of Proteome Research 10:11, 5232-5241
CrossRef4
Andrea Schweitzer, Shirley K. Knauer, Roland H. Stauber. (2009) Nuclear receptors in head and neck cancer: current knowledge and perspectives. International Journal of Cancern/a-n/a
CrossRef
